Characterising gadofosveset for use in quantitative MRI studies

Background: Gadofosveset is a clinically approved gadolinium-based MRI contrast agent that displays altered pharmacokinetic properties due to its high albumin-binding affinity (around 90% binds at low concentration), although the improved effectiveness due to binding reduces as field strength increases. With the trend for increasing clinical magnetic field strengths, it is important that gadofosveset is fully characterised at higher fields. It may then be possible to utilise the macromolecular properties of bound gadofosveset in tracer kinetic modelling for assessment of functional parameters.
Aims: This study aimed to characterise gadofosveset, in vitro, at relevant field strengths, develop a method for acquiring blood concentration measurements, and assess several novel techniques utilising the agent’s binding affinity. The study was extended to include gadoxetate and gadobenate, gadolinium agents with a lower albumin-binding affinity, to provide a broader view of the influence of albumin binding.
Results: Relaxivities were calculated from in vitro measurements in the presence and absence of albumin, including bound relaxivity values at high field that have not previously been published. Extending the conventional model assumption of a single binding site to include up to three bound molecules improved the model fit for gadofosveset at low fields. A technique for using micro-samples of blood to measure gadolinium levels was successfully demonstrated in vitro, which may enable improved accuracy in dynamic studies. A macromolecule-sensitive technique (spin locking) gave a significant increase in albumin-bound gadofosveset relaxation rates at high field. A method for using gadofosveset as a biomarker for albumin was successfully applied in vitro, and the feasibility of in vivo implementation was assessed.
Conclusions: This in vitro characterisation of gadofosveset across a range of field strengths may inform future in vivo tracer kinetic modelling studies. Several novel applications for exploiting these characteristics have been successfully demonstrated in vitro, and warrant further in vivo investigation.